This award will allow Kelly Wade, M.D., Ph.D., to continue her career development as a pediatric clinical pharmacologist, with a focus on improving pharmacotherapy for critically ill newborns. Dr. Wade, a neonatologist at the Children's Hospital of Philadelphia (CHOP) and Instructor of Pediatrics at the University of Pennsylvania (UPENN), has a strong background in pediatric research and a passion for improving the clinical outcomes of critically ill neonates. The rapid developmental changes that occur in the newborn period directly impact upon the therapeutic and toxic effects of drug therapy. However, critically ill infants often receive drugs that lack appropriate dosing guidelines and therefore are exposed to the risks of excessive toxicity or suboptimal therapy. Dr. Wade will develop a rigorous yet feasible approach to pharmacokinetic pharmacodynamic (PKPD) analysis of select drugs in infants in order to develop pharmacologically rational, safe, and effective dosing guidance. Her research will specifically focus on the treatment of select high risk infectious diseases. Despite the high rate of morbidity and mortality, therapy for fungal infections and influenza infections in newborns and infants remains poorly studied. Dr. Wade will lead two multicentered PPRU protocols: the first is an evaluation of the pharmacokinetics of fluconazole, and the second will be a pharmacokinetic analysis of oseltamivir in infants. A comprehensive training program, through didactic and mentored research, will provide in-depth training in pediatric clinical pharmacology emphasizing pharmacometrics, dose response relationships, PKPD modeling, and clinical trial design and simulation. The impact of developmental, physiologic, and metabolic influences on drug disposition will be explored. As a component of her training, Dr. Wade will complete a Masters Degree in Clinical Epidemiology and Biostatistics at UPENN. Her advisory committee will provide mentorship from senior investigators in neonatology, pharmacology, infectious disease, and clinical epidemiology. Upon completion of her MSCIDA supported training, Dr. Wade will continue to develop investigator initiated research protocols and pursue independently funded research in pediatric clinical pharmacology. (Lay summary) Infections are a leading cause of serious illness in babies. Dr. Wade will perform research to determine how to optimize the dosing of drugs used to treat infections caused by yeast and the influenza (flu) virus. [unreadable] [unreadable] [unreadable]